Review
Medicine, Research & Experimental
Lijuan Mao, Wei Wei, Jingyu Chen
Summary: Glucocorticoids (GCs) are steroid hormones that regulate various homeostatic functions in the body through the binding of glucocorticoid receptor (GR). GR signals are biased, with variations in different tissue cells, disease states, and ligands. This bias regulation of GR signaling depends on ligand-induced metameric regulation, protein post-translational modifications, assembly at response elements, context-specific assembly, and intercellular differences. Selective GR agonists and modulators (SEGRAMs) have been developed to bias therapeutic outcomes towards expected effects by influencing GR-mediated gene expression. This paper reviews the bias regulation and mechanism of GR, as well as the progress in drug research.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Review
Medicine, General & Internal
Huanming Huang, Wenqing Wang
Summary: This article provides an overview of the molecular mechanisms of glucocorticoid resistance (GCR), focusing on NR3C1 gene mutations and impaired glucocorticoid receptor (GR) signaling. The study found that NR3C1 gene mutations are the main cause of primary GCR, while secondary GCR is caused by abnormalities in GC signaling pathways, such as decreased expression of GR, impaired nuclear translocation of GR, and impaired binding of GR to GC and target genes. However, most of the current research is focused on the expression level of GR, with relatively few studies on other mechanisms, and there are few reported methods for improving GC sensitivity.
EUROPEAN JOURNAL OF CLINICAL INVESTIGATION
(2023)
Article
Multidisciplinary Sciences
Li-Hua Zhao, Qian He, Qingning Yuan, Yimin Gu, Xinheng He, Hong Shan, Junrui Li, Kai Wu, Yang Li, Wen Hu, Kai Wu, Jianhua Shen, H. Eric Xu
Summary: A study reports an orally available small-molecule agonist that binds between a G protein and its receptor, and characterizes this new binding mode.
Article
Multidisciplinary Sciences
Li-Hua Zhao, Qian He, Qingning Yuan, Yimin Gu, Xinheng He, Hong Shan, Junrui Li, Kai Wang, Yang Li, Wen Hu, Kai Wu, Jianhua Shen, H. Eric Xu
Summary: This study reports a new binding mode between a G protein and its receptor, involving a specific small-molecule agonist. The high-resolution structure of the complex is determined, providing insights for designing small-molecule agonists for class B G-protein-coupled receptors.
Article
Biochemistry & Molecular Biology
Jacobus C. Buurstede, Susana N. Paul, Karolien De Bosscher, Onno C. Meijer, Jan Kroon
Summary: Glucocorticoids exert their effects by activating the glucocorticoid receptor (GR) throughout the body. This study investigated the interaction between glucocorticoids and androgen signaling in the liver transcriptome. The results showed that a substantial proportion of the hepatic transcriptome is androgen-dependent after chronic exposure, while the effects of glucocorticoids are largely androgen-independent after acute exposure. The study suggests that prolonged glucocorticoid exposure may upregulate androgen receptor expression, leading to androgen dependence not driven by direct interactions between the androgen receptor and glucocorticoid receptor.
Article
Pharmacology & Pharmacy
Mengru Bai, Mingyang Chen, Qingquan Zeng, Shuanghui Lu, Ping Li, Zhiyuan Ma, Nengming Lin, Caihong Zheng, Hui Zhou, Su Zeng, Dongli Sun, Huidi Jiang
Summary: The elevated levels of corticosterone/cortisol during pregnancy accelerate fatty acid uptake into hepatocytes via activation of GR and its target gene, CD36, leading to liver lipid accumulation and hypertriglyceridemia. This finding may contribute to the prevention of severe hypertriglyceridemia and associated pregnancy complications.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Alberto Dinarello, Annachiara Tesoriere, Paolo Martini, Camilla Maria Fontana, Davide Volpato, Lorenzo Badenetti, Francesca Terrin, Nicola Facchinello, Chiara Romualdi, Oliana Carnevali, Luisa Dalla Valle, Francesco Argenton
Summary: In this study, zebrafish mutant lines and transgenic models were used to analyze the mechanism of action of glucocorticoids. The differences in gene expression patterns between different mutant lines revealed a complex network of GC-dependent transcription. The study also showed that the glucocorticoid receptor GR plays a crucial role in the transcriptional activity of Stat3, and both glucocorticoids and the mineralocorticoid receptor MR are necessary for the correct transcription of certain target genes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Chi-Nga Chow, Chien-Wen Yang, Nai-Yun Wu, Hung-Teng Wang, Kuan-Chieh Tseng, Yu-Hsuan Chiu, Tzong-Yi Lee, Wen-Chi Chang
Summary: PlantPAN 4.0 is an integrative resource for constructing transcriptional regulatory networks for diverse plant species. It provides extensive gene annotation and promoter sequences, helping users understand evolutionary differences and similarities among species and identify conserved non-coding sequences in homologous genes. Additionally, it offers a comprehensive collection of transcription factor binding site information and improved ChIP-seq data analysis tools for reconstructing gene regulatory networks.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Chemistry, Medicinal
Xueping Hu, Jinping Pang, Changwei Chen, Dejun Jiang, Chao Shen, Xin Chai, Liu Yang, Xujun Zhang, Lei Xu, Sunliang Cui, Tingjun Hou, Dan Li
Summary: This study identified a group of selective glucocorticoid receptor modulators (SGRMs) through virtual screening, which showed good transrepression activity without transactivation activity, suggesting their potential as novel anti-inflammatory drugs.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Review
Genetics & Heredity
Guanping Chen, Shudi Zhao, Nan Chen, Xiaofeng Wu
Summary: This review comprehensively summarizes the molecular mechanism underlying the hyperexpression of polyhedrin gene in baculovirus, focusing on the promoter and transcription regulation, mRNA structure and translation regulation, as well as the regulators influencing gene expression. This understanding can provide guidance for enhancing the expression efficiency of foreign proteins using the baculovirus expression vector system.
Review
Cell Biology
Davide Marchi, Fredericus J. M. van Eeden
Summary: Glucocorticoids are essential for regulating physiological processes, but chronic steroid use may lead to limited therapeutic benefits. Understanding how to modulate glucocorticoid receptor activity is crucial for minimizing side effects and improving treatment outcomes.
Article
Engineering, Environmental
Qing Zhou, Yanhong Shen, Liben Chou, Jing Guo, Xiaowei Zhang, Wei Shi
Summary: This study developed a workflow using effect-directed analysis (EDA) to identify responsible contaminants in dust samples. GR antagonistic potencies were detected in 34.8% of the dust samples from 23 cities in China. The potencies were reduced after bioaccessible extraction. A high number of candidate chemical structures were removed using in silico candidate selection. Di-n-butyl phthalate, diisobutyl phthalate, and nicotine were found to be responsible for the activities in both exhaustive and bioaccessible extracts of dust samples.
ENVIRONMENTAL SCIENCE & TECHNOLOGY
(2022)
Review
Endocrinology & Metabolism
Florian Le Billan, Gloria Umogbai, Carolyn L. Cummins
Summary: Steroid hormones not only regulate gene transcription but also modulate the alternative splicing of pre-mRNA, acting through binding to nuclear receptors. The effect of steroid hormones on alternative splicing is time-, gene-, and tissue-specific. Mechanisms by which steroid hormones regulate alternative splicing include the recruitment of dual-function proteins, transcriptional regulation of splicing factor levels, alternative splicing of splicing factors or transcription factors, and regulation of elongation rate.
Article
Endocrinology & Metabolism
Shao-Yang Bu, Yan-Yu Zhang, Xian Zhang, Tian-Xiu Li, De-Cai Zheng, Ze-Xiang Huang, Qian Wang
Summary: The stress hormone cortisol can regulate the expression of the kiss2 gene in yellowtail clownfish by binding to the glucocorticoid receptor (GR). Kiss neurons in the yellowtail clownfish express glucocorticoid receptors in different brain regions. The promoter of the kiss2 gene in yellowtail clownfish contains binding sites for glucocorticoid receptors, estrogen receptors, androgen receptors, progesterone receptors, AP1, and C/EBP. The transcription of the kiss2 gene can be enhanced by cortisol treatment through the GRE-dependent GR pathway.
FRONTIERS IN ENDOCRINOLOGY
(2022)
Article
Clinical Neurology
Jelena Bakusic, Manosij Ghosh, Andrea Polli, Bram Bekaert, Wilmar Schaufeli, Stephan Claes, Lode Godderis
Summary: The study revealed that job stress was associated with increased levels of cortisol and cortisone in burnout participants. Changes in DNA methylation of the NR3C1 and SLC6A4 genes were observed in burnout individuals, and some of these methylation changes correlated with burnout symptoms. Increased methylation in a specific CpG in the SLC6A4 gene moderated the association between job stress and burnout, while DNA methylation in this CpG was also associated with increased cortisol levels. Furthermore, average methylation of NR3C1 was negatively associated with cortisone levels.
JOURNAL OF AFFECTIVE DISORDERS
(2021)